This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step ... See more...

Aliases for LNPEP Gene

Aliases for LNPEP Gene

  • Leucyl And Cystinyl Aminopeptidase 2 3 5
  • Placental Leucine Aminopeptidase 2 3 4
  • Cystinyl Aminopeptidase 2 3 4
  • P-LAP 2 3 4
  • IRAP 2 3 4
  • Insulin-Regulated Membrane Aminopeptidase 3 4
  • Insulin-Responsive Aminopeptidase 3 4
  • Leucyl-Cystinyl Aminopeptidase 3 4
  • Oxytocinase 3 4
  • EC 3.4.11.3 4 51
  • PLAP 2 3
  • CAP 2 3
  • Insulin-Regulated Aminopeptidase 3
  • Leucyl/Cystinyl Aminopeptidase 2
  • Angiotensin IV Receptor 3
  • AT (4) Receptor 3
  • Vasopressinase 3
  • EC 3.4.11'); 51
  • EC 3.4.11 51
  • Otase 3
  • LNPEP 5
  • OTASE 4
  • OTase 4

External Ids for LNPEP Gene

Previous GeneCards Identifiers for LNPEP Gene

  • GC05P095502
  • GC05P096736
  • GC05P096300
  • GC05P096346
  • GC05P096347
  • GC05P096297
  • GC05P096272
  • GC05P091461

Summaries for LNPEP Gene

Entrez Gene Summary for LNPEP Gene

  • This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for LNPEP Gene

LNPEP (Leucyl And Cystinyl Aminopeptidase) is a Protein Coding gene. Diseases associated with LNPEP include Gestational Diabetes Insipidus and Placental Site Trophoblastic Tumor. Among its related pathways are Vesicle-mediated transport and Innate Immune System. Gene Ontology (GO) annotations related to this gene include metallopeptidase activity and aminopeptidase activity. An important paralog of this gene is ERAP1.

UniProtKB/Swiss-Prot Summary for LNPEP Gene

  • Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.

Tocris Summary for LNPEP Gene

Gene Wiki entry for LNPEP Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LNPEP Gene

Genomics for LNPEP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LNPEP Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LNPEP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LNPEP

Top Transcription factor binding sites by QIAGEN in the LNPEP gene promoter:
  • AML1a
  • Egr-4
  • HOXA3
  • Meis-1
  • Meis-1a
  • Meis-1b
  • Sp1
  • SREBP-1c
  • TBP

Genomic Locations for LNPEP Gene

Latest Assembly
chr5:96,934,859-97,037,513
(GRCh38/hg38)
Size:
102,655 bases
Orientation:
Plus strand

Previous Assembly
chr5:96,271,784-96,373,217
(GRCh37/hg19 by Entrez Gene)
Size:
101,434 bases
Orientation:
Plus strand

chr5:96,271,098-96,373,219
(GRCh37/hg19 by Ensembl)
Size:
102,122 bases
Orientation:
Plus strand

Genomic View for LNPEP Gene

Genes around LNPEP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LNPEP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LNPEP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LNPEP Gene

Proteins for LNPEP Gene

  • Protein details for LNPEP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UIQ6-LCAP_HUMAN
    Recommended name:
    Leucyl-cystinyl aminopeptidase
    Protein Accession:
    Q9UIQ6
    Secondary Accessions:
    • O00769
    • Q15145
    • Q59H76
    • Q9TNQ2
    • Q9TNQ3
    • Q9UIQ7

    Protein attributes for LNPEP Gene

    Size:
    1025 amino acids
    Molecular mass:
    117349 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer. Binds tankyrases 1 and 2.
    SequenceCaution:
    • Sequence=BAA09436.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD92120.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for LNPEP Gene

    Alternative splice isoforms for LNPEP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LNPEP Gene

Selected DME Specific Peptides for LNPEP Gene

Q9UIQ6:
  • KLDLVAIPDF
  • DEPAFKATF
  • WWNDLWLNE
  • GAMENWG
  • STYLVAF
  • GYYIVHY
  • WFGNLVT
  • HELAHQWFG
  • TWTLQKG
  • WLNEGFA
  • VAIPDFEAGAMENWGL

Post-translational modifications for LNPEP Gene

  • The pregnancy serum form is derived from the membrane-bound form by proteolytic processing.
  • N-glycosylated.
  • Glycosylation at Asn145, Asn184, Asn215, Asn256, Asn266, Asn368, Asn374, Asn448, Asn525, Asn578, Asn598, Asn664, Asn682, Asn760, Asn834, Asn850, and Asn989
  • Ubiquitination at Lys75
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for LNPEP Gene

Domains & Families for LNPEP Gene

Gene Families for LNPEP Gene

Protein Domains for LNPEP Gene

InterPro:
Blocks:
  • Membrane alanyl dipeptidase (M1) family signature
ProtoNet:

Suggested Antigen Peptide Sequences for LNPEP Gene

GenScript: Design optimal peptide antigens:
  • Placental leucine aminopeptidase (LCAP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UIQ6

UniProtKB/Swiss-Prot:

LCAP_HUMAN :
  • Belongs to the peptidase M1 family.
Family:
  • Belongs to the peptidase M1 family.
genes like me logo Genes that share domains with LNPEP: view

Function for LNPEP Gene

Molecular function for LNPEP Gene

UniProtKB/Swiss-Prot Function:
Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Release of an N-terminal amino acid, Cys-|-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however.; EC=3.4.11.3; Evidence={ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:1731608};.

Enzyme Numbers (IUBMB) for LNPEP Gene

Phenotypes From GWAS Catalog for LNPEP Gene

Gene Ontology (GO) - Molecular Function for LNPEP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004177 aminopeptidase activity EXP,TAS 15691326
GO:0005515 protein binding IPI 25416956
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity TAS 9177475
GO:0008270 zinc ion binding TAS,IBA 21873635
genes like me logo Genes that share ontologies with LNPEP: view
genes like me logo Genes that share phenotypes with LNPEP: view

Animal Models for LNPEP Gene

MGI Knock Outs for LNPEP:

Animal Models for research

miRNA for LNPEP Gene

miRTarBase miRNAs that target LNPEP

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LNPEP

Clone products for research

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for LNPEP Gene

Localization for LNPEP Gene

Subcellular locations from UniProtKB/Swiss-Prot for LNPEP Gene

Cell membrane. Single-pass type II membrane protein. Note=In brain only the membrane-bound form is found. The protein resides in intracellular vesicles together with GLUT4 and can then translocate to the cell surface in response to insulin and/or oxytocin. Localization may be determined by dileucine internalization motifs, and/or by interaction with tankyrases.
[Leucyl-cystinyl aminopeptidase, pregnancy serum form]: Secreted. Note=During pregnancy serum levels are low in the first trimester, rise progressively during the second and third trimester and decrease rapidly after parturition.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LNPEP gene
Compartment Confidence
extracellular 5
cytosol 5
plasma membrane 4
endosome 4
lysosome 4
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
golgi apparatus 2
cytoskeleton 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for LNPEP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005737 cytoplasm IBA 21873635
GO:0005765 lysosomal membrane HDA 17897319
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IBA,ISS --
genes like me logo Genes that share ontologies with LNPEP: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for LNPEP Gene

Pathways & Interactions for LNPEP Gene

genes like me logo Genes that share pathways with LNPEP: view

Pathways by source for LNPEP Gene

SIGNOR curated interactions for LNPEP Gene

Is activated by:

Gene Ontology (GO) - Biological Process for LNPEP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS --
GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent TAS --
GO:0006508 proteolysis TAS,IBA 21873635
GO:0007165 signal transduction IBA 21873635
GO:0007267 cell-cell signaling TAS 8550619
genes like me logo Genes that share ontologies with LNPEP: view

Drugs & Compounds for LNPEP Gene

(25) Drugs for LNPEP Gene - From: ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zinc Approved, Investigational Pharma 1687
Oxytocin Approved, Vet_approved Pharma Involved in uterine contraction and lactation 654
Vasopressin Approved Pharma 0
bestatin Pharma Aminopeptidase inhibitor 0
Tosedostat (CHR2797) Pharma Aminopeptidase inhibitor 0

(7) Additional Compounds for LNPEP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(2) ApexBio Compounds for LNPEP Gene

Compound Action Cas Number
Bestatin Aminopeptidase inhibitor 58970-76-6
Tosedostat (CHR2797) Aminopeptidase inhibitor 238750-77-1
genes like me logo Genes that share compounds with LNPEP: view

Drug products for research

Transcripts for LNPEP Gene

mRNA/cDNA for LNPEP Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LNPEP

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for LNPEP Gene

No ASD Table

Relevant External Links for LNPEP Gene

GeneLoc Exon Structure for
LNPEP

Expression for LNPEP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LNPEP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for LNPEP Gene

This gene is overexpressed in Lymph node (15.3) and Nasal epithelium (9.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LNPEP Gene



Protein tissue co-expression partners for LNPEP Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LNPEP

SOURCE GeneReport for Unigene cluster for LNPEP Gene:

Hs.527199

mRNA Expression by UniProt/SwissProt for LNPEP Gene:

Q9UIQ6-LCAP_HUMAN
Tissue specificity: Highly expressed in placenta, heart, kidney and small intestine. Detected at lower levels in neuronal cells in the brain, in skeletal muscle, spleen, liver, testes and colon.

Evidence on tissue expression from TISSUES for LNPEP Gene

  • Nervous system(4.5)
  • Liver(4.4)
  • Muscle(2.7)
  • Kidney(2.5)
  • Heart(2.5)
  • Spleen(2.4)
  • Blood(2.3)
  • Intestine(2.1)
  • Adrenal gland(2.1)
genes like me logo Genes that share expression patterns with LNPEP: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for LNPEP Gene

Orthologs for LNPEP Gene

This gene was present in the common ancestor of animals.

Orthologs for LNPEP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LNPEP 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LNPEP 30 31
  • 90.55 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LNPEP 30 31
  • 87.45 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Lnpep 30 17 31
  • 87.19 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia LNPEP 31
  • 79 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia LNPEP 31
  • 69 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LNPEP 30 31
  • 70.18 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LNPEP 31
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lnpep 30
  • 62.59 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC69084 30
Zebrafish
(Danio rerio)
Actinopterygii lnpep 30 31
  • 58.87 (n)
OneToOne
wufb73h12 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG11951 32
  • 39 (a)
CG8773 32
  • 35 (a)
sda 32
  • 30 (a)
CG3502 32
  • 29 (a)
BG:DS00365.1 32
  • 27 (a)
CG2111 32
  • 26 (a)
CG5849 32
  • 26 (a)
CG4467 31
  • 22 (a)
OneToMany
CG6071 32
  • 22 (a)
Worm
(Caenorhabditis elegans)
Secernentea Y67D8C.9 32
  • 34 (a)
R03G8.4 32
  • 29 (a)
R03G8.6 32
  • 29 (a)
Y42A5A.1 32
  • 28 (a)
F49B2.6 31
  • 27 (a)
OneToMany
T07F10.1 32
  • 26 (a)
T16G12.1 32
  • 26 (a)
AC3.5 32
  • 22 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 34 (a)
OneToMany
Species where no ortholog for LNPEP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for LNPEP Gene

ENSEMBL:
Gene Tree for LNPEP (if available)
TreeFam:
Gene Tree for LNPEP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LNPEP: view image

Paralogs for LNPEP Gene

Paralogs for LNPEP Gene

(9) SIMAP similar genes for LNPEP Gene using alignment to 1 proteins:

  • LCAP_HUMAN
genes like me logo Genes that share paralogs with LNPEP: view

Variants for LNPEP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LNPEP Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs11746232 - p.Ile963Val
rs12520455 - p.Asn594Ile
rs17087233 - p.Ser913Thr
rs2303138 - p.Ala763Thr
rs3797799 - p.Ser86Pro

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LNPEP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for LNPEP Gene

Variant ID Type Subtype PubMed ID
esv2730489 CNV deletion 23290073
esv2730490 CNV deletion 23290073
esv2740869 CNV deletion 23290073
esv3605871 CNV loss 21293372
esv3890674 CNV gain 25118596
nsv1021263 CNV loss 25217958
nsv1028741 CNV gain 25217958
nsv1123970 CNV deletion 24896259
nsv1131903 CNV deletion 24896259
nsv507276 OTHER sequence alteration 20534489
nsv598962 CNV gain 21841781
nsv598963 CNV gain 21841781
nsv819519 CNV gain 19587683
nsv980700 CNV duplication 23825009

Variation tolerance for LNPEP Gene

Residual Variation Intolerance Score: 6.39% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.22; 88.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LNPEP Gene

Human Gene Mutation Database (HGMD)
LNPEP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LNPEP

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LNPEP Gene

Disorders for LNPEP Gene

MalaCards: The human disease database

(15) MalaCards diseases for LNPEP Gene - From: COP and GCD

Disorder Aliases PubMed IDs
gestational diabetes insipidus
  • diabetes insipidus gestational
placental site trophoblastic tumor
  • placental site trophoblastic tumour
diabetes insipidus, neurohypophyseal
  • diabetes insipidus, primary central; cdi
trophoblastic neoplasm
  • trophoblastic tumor
choriocarcinoma
  • chorioepithelioma
- elite association - COSMIC cancer census association via MalaCards
Search LNPEP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for LNPEP

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with LNPEP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for LNPEP Gene

Publications for LNPEP Gene

  1. Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. (PMID: 8550619) Rogi T … Tomoda Y (The Journal of biological chemistry 1996) 2 3 4 23
  2. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. (PMID: 11707427) Albiston AL … Chai SY (The Journal of biological chemistry 2001) 3 4 23
  3. Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides. (PMID: 11389728) Matsumoto H … Tsujimoto M (European journal of biochemistry 2001) 3 4 23
  4. Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21. (PMID: 10759854) Rasmussen TE … Kristensen T (European journal of biochemistry 2000) 3 4 23
  5. The complete amino acid sequence of human placental oxytocinase. (PMID: 9177475) Laustsen PG … Kristensen T (Biochimica et biophysica acta 1997) 3 4 23

Products for LNPEP Gene

Sources for LNPEP Gene